Electrochemical process for the preparation of acetals of 2-haloaldehydes

ABSTRACT

Electrolysis of a substantially anhydrous electrolysis medium comprising a primary alcohol having at least one beta-hydrogen atom and anhydrous hydrogen halide selected from the group consisting of hydrogen chloride and hydrogen bromide yields acetals of 2-haloaldehydes corresponding to the primary alcohol.

BACKGROUND OF THE INVENTION

This invention relates to a process for the preparation of acetals of2-haloaldehydes, or 2-haloaldehyde acetals or simply 2-haloacetals, bysubjecting primary alcohols having at least one beta-hydrogen atom toelectrolysis under substantially anhydrous conditions in the presence ofanhydrous hydrogen halide selected from the group consisting of hydrogenchloride and hydrogen bromide in an electrolytic cell. Exemplary of the2-haloaldehyde acetals is chloroacetal (chloroacetaldehyde diethylacetal) prepared from absolute ethanol and anhydrous hydrogen chloride.The products are useful as versatile bifunctional reagents. They canreact either as alkyl halides or as sources of the aldehydefunctionality, or both.

The preparation of acetals of 2-haloaldehydes, particularly acetals of2-chloroaldehydes has been previously described in the prior art. Bievreet al, Bulletin des Societes Chimiques Belges, 68, 550-557 (1959)describes the preparation of chloroacetaldehyde diethyl acetal bytreating ethyl alcohol with chlorine gas. Chattaway et al, Journal ofthe Chemical Society, 125, 1097-1101 (1924); Fritsch, Annalen, 279,288-300 (1894); and Lieben, Annalen, 104, 114-115 (1857) describessimilar procedures. Overall, the reaction proceeds according todiagrammatically simplified reaction (1).

    3CH.sub.3 CH.sub.2 OH + 2Cl.sub.2 → ClCH.sub.2 CH(OCH.sub.2 CH.sub.3).sub.2 + 3HCl + H.sub.2 O                        (1)

However, chemical routes involving these raw materials suffer from thedisadvantage that the reaction produces three moles of hydrogen chlorideper mole of acetal. The disposal of this large volume of hydrogenchloride presents obvious difficulties which significantly detract fromthe attractiveness of such chemical processes for large scale reactions.

It has now been discovered tha the difficulties and disadvantagesassociated with the prior art chemical processes are overcome by theprocess of the present invention which represents a substantialimprovement in the sense that

(A) HYDROGEN HALIDE IS CONSUMED DURING THE REACTION, THEREBY ALLEVIATINGTHE PROBLEM OF DISPOSAL OF LARGE VOLUMES OF HYDROGEN HALIDE; AND

(B) ONLY INNOCUOUS CO-PRODUCTS--HYDROGEN, WHICH MAY BE BURNED TO WATER,AND WATER ITSELF--ARE PRODUCED DURING THE REACTION.

Various other advantages of this invention will become apparent from theaccompanying description and claims.

SUMMARY OF THE INVENTION

This invention involves a process for the preparation of acetals of2-haloaldehydes. The process comprises subjecting a substantiallyanhydrous liquid electrolysis medium comprising a primary alcohol havingat least one beta-hydrogen atom and anhydrous hydrogen halide selectedfrom the group consisting of hydrogen chloride and hydrogen bromide toelectrolysis in an electrolytic cell to yield the acetal of the2-haloaldehyde corresponding to the primary alcohol.

The 2-haloaldehyde acetal products obtained in the present process areeasily recovered by neutralizing unreacted hydrogen halide with calciumcarbonate and removing the excess primary alcohol and/or added solvent(when employed). The product can be purified, if desired by distillationat appropriate temperatures and pressures.

DETAILED DESCRIPTION OF THE INVENTION

The electrochemical preparation of acetals of 2-haloaldehydes of thepresent process is conveniently represented by reactions (2) through (6)wherein R¹ and R² are individually selected from hydrogen, alkyl, andphenyl; R³ represents a hydrocarbyl moiety corresponding to the primaryalcohol undergoing conversion, R¹ R² CHCH₂ --, or methyl; and Xrepresents a halogen selected from the group consisting of chlorine andbromine.

    ANODE REACTION 4X.sup.31 → 2X.sub.2 + 4e.sup.-      ( 2)

    SOLUTION REACTION X.sub.2 + R.sup.1 R.sup.2 CHCH.sub.2 OH → R.sup.1 R.sup.2 CHCHO + 2H.sup.+ + 2X.sup.-                       ( 3)

    r.sup.1 r.sup.2 chcho + 2r.sup.3 oh ⃡ r.sup.1 r.sup.2 chch(or.sup.3).sub.2 + h.sub.2 o                          (4) ##STR1##

    cathode reaction 4h.sup.+ + 4e.sup.- → 2H.sub.2     ( 6)

The net effect of reactions (2) through (6) are summarized as shown inreaction (7). ##STR2##

While not desiring to be bound by the theory of the present invention,it is believed that the present invention, as illustrated by reactions(2) through (6), comprises

(a) anodic generation of molecular halogen from the halide ion providedby the anhydrous hydrogen halide;

(b) oxidative reaction of the molecular halogen with the primary alcoholto form the corresponding aldehyde;

(c) acid-catalyzed conversion of the aldehyde to the acetal; and

(d) halogenation of the acetal to form the 2-haloaldehyde acetalproduct.

Cathodic reduction of hydrogen ions (protons) completes theelectrochemical reaction.

In accordance with the process of the present invention, theelectrochemical preparation of acetals of 2-haloaldehydes is carried outby subjecting a substantially anhydrous liquid electrolysis mediumcomprising a primary alcohol having at least one beta-hydrogen atom andanhydrous hydrogen halide selected from the group consisting of hydrogenchloride and hydrogen bromide to electrolysis in an electrolytic cell toyield the acetal of the 2-haloaldehyde corresponding to the primaryalcohol.

The term "substantially anhydrous" is employed herein to indicate thepresence of only nominal amounts of water. It will be noted that whilethe presence of water in the electrolysis medium on the order of about 5percent by weight may be tolerated, the maximum water content ispreferably no more than about 1 percent to about 2 percent by weight,with even lower values being most preferred.

The primary alcohols of most interest for use in the present processinclude those up to C₂₀, although any primary alcohol having at leastone beta-hydrogen atom may be used, if desired. It will be noted,however, that the higher molecular weight alcohols for example, greaterthan C₆, will generally require added solvent (other than excesssubstrate primary alcohol) as discussed hereinbelow.

Exemplary of the primary alcohols suitable for use in the presentprocess are ethanol, 1-propanol (n-propyl alcohol), 1-butanol (n-butylalcohol), 2-methyl-1-propanol (isobutyl alcohol), 3-methyl-1-butanol,3,5-dimethyl-1-hexanol, 5,5-dimethyl-1-hexanol, 2-phenylethanol,2,2-diphenylethanol, and the like.

The present reaction can be effected in the presence of an added solvent(other than excess substrate primary alcohol) for the primary alcoholand the anhydrous hydrogen halide. This, of course, permits theemployment of high molecular weight alcohols, for example, greater thanC₆, which have low dielectric constants and, in particular, may besolids at appropriate reaction temperatures.

Suitable added solvents which can be employed are preferably relativelyinert under reaction conditions. By "relatively inert," it is meant thatthe added solvents, under process conditions, (a) do not preferentiallyundergo electrochemical reaction and (b) do not significantly react withthe anhydrous hydrogen halide.

The latter requirement [(b)] is especially significant in that severalof the usual electrochemical solvents--amines, ethers, cycliccarbonates, for example--react with anhydrous hydrogen halide, andtherefore are not suitable. Even acetonitrile and dimethylformamide,perhaps the most common aprotic electrochemical solvents, react with thehydrogen halide and alcohol solution. Therefore, as a practical matter,neither acetonitrile nor dimethylformamide is preferred. Methylenechloride, however, is suitable and gives results comparable with thoseobtained when using excess primary alcohol as solvent. (Compare Examples3 and 12, Table 1.) And although its volatility is an added advantageduring work-up of the reaction solution, its low dielectric constant isslightly disadvantageous.

Another solvent which surprisingly is also suitable for use is methanol.It has a high dielectric constant (32.63 at 25° C.); is oxidized onlywith difficulty by anodically generated halogen (see Example 14, Table1); has no beta hydrogen atoms; and is reasonably volatile. It will berecognized, however, that when methanol is employed (in excess) as theadded solvent, the acetals of the 2-haloaldehydes will be dimethylacetals. This fact presents no difficulty, however, since one acetalmoiety is essentially eqivalent to another acetal moiety as a source ofan aldehyde functionality. Indeed, methanol is a particularlyadvantageous solvent when the substrate primary alcohol is a highmolecular weight alcohol.

The reactions which occur when methanol is employed as the added solventcan be illustrated by reactions (8) through (10) using hydrogen chlorideas the hydrogen halide. ##STR3##

It will be apparent of course that when R³ represents methyl and Xrepresents chlorine, reaction (8) is equivalent to reaction (7).

As illustrated in reaction (8), the formation of the dimethyl acetaldepends primarily on the use of a large excess of methanol, although theacid-catalyzed equilibrium between the three possible acetals asillustrated in reactions (9) and (10) is also important. The latterequilibrium reactions are important because consumption of the substrateprimary alcohol displaces these equilibria to the right (to ultimatelyproduce the dimethyl acetal) as the reaction progresses.

From the discussion hereinabove, it is apparent that when an addedsolvent is desired and when the dimethyl acetal product is suitable,methanol is the solvent of choice.

Added primary alcohol (other than the substrate primary alcohol andmethanol) may be suitable for use as added solvent,--that is, mixturesof primary alcohols--however, such mixtures of primary alcohols wouldgive difficult to separate mixtures of products. Therefore, as apractical matter, such mixtures of primary alcohols are to be avoided.

The anhydrous hydrogen halides suitable for use in the present processare selected from the group consisting of hydrogen chloride and hydrogenbromide. Of these, hydrogen chloride is preferred because of the greaterchemical reactivity of chlorine with the substrate primary alcohol. Thisgreater chemical reactivity prevents accumulation of molecular chlorinein the liquid electrolysis medium, and thereby minimizes uselessreduction to chloride ions at the cathode. This uselessoxidation-reduction equilibrium, when encountered, results in a decreasein current efficiency. Iodine, of course, has a very great tendency toundergo this oxidation-reduction equilibrium. Indeed hydrogen iodide isgenerally not suitable for use in the present process in that when it isemployed as the hydrogen halide the reaction fails to yield the desiredacetal of the 2-iodoaldehyde corresponding to the primary alcohol.

Bromine, as expected, is intermediate between chlorine and iodine in itstendency to undergo an oxidation-reduction equilibrium. Hydrogen bromideis also somewhat more expensive than is hydrogen chloride. However, whenhydrogen bromide is employed as the hydrogen halide, the reactionproceeds in a very satisfactory manner to yield the acetal of the2-bromoaldehyde corresponding to the primary alcohol. Accordingly,hydrogen bromide, while less preferred than hydrogen chloride is quitesuitable for use as the hydrogen halide.

As will be apparent, when the reaction is carried out in the absence ofadded solvent, the concentration of the primary alcohol is of noconsequence. And even when an added solvent is used, the concentrationis not critical and can vary within fairly wide limits. When methylenechloride is the added solvent, a convenient concentration range isbetween about 5 percent up to about 25 percent or more by weight of theelectrolysis medium, or on a molar basis, between about 1.0 molar andabout 6.0 molar. As noted, however, the concentration is not criticaland any convenient concentration can be used so long as sufficientcurrent can pass to permit the reaction to proceed at a reasonable rate.

When methanol is employed as the added solvent, the concentrationbecomes slightly more critical in that, as noted hereinabove, formationof the dimethyl acetal depends primarily on the presence of a largeexcess of methanol. The molar ratio of methanol to primary alcohol mustbe at least 2:1 as shown in reaction (8). A molar ratio range betweenabout 4:1 and about 24:1 is preferred, however, with a ratio of about8:1 being most preferred. And while the upper limit (24:1) is notcritical, for reasons of practicality higher ratios, which would produceextremely dilute reaction solutions (and likely require larger amountsof hydrogen halide) and thereby make isolation of the 2-haloaldehydeacetal product more tedious and time-consuming, are not generallyemployed.

Expressed on a molar basis, a suitable and convenient concentrationrange is between about 1.0 molar and about 6.0 molar, with about 3.0molar being generally preferred when methanol is employed as the addedsolvent.

Thus, when an added solvent is employed, a molar concentration of thesubstrate primary alcohol in the added solvent of about 1.0 molar toabout 6.0 molar is generally preferred.

The concentration of the hydrogen halide is not narrowly critical,although, as noted hereinabove, low concentrations [particularly inconjunction with low temperatures (<30° C.)] tend to favor production(albeit in only minor amounts) of unsubstituted (non-halogenated)acetal. A suitable molar ratio of hydrogen halide to the substrateprimary alcohol is between about 1:0.1 and about 1:10. The higher molarratio (1:0.1) limit, however, is imposed more for practical reasons thanfor criticality of process conditions in that isolation of the productrequires neutralization of unreacted hydrogen halide. A convenientrange, therefore, is between about 1:0.5 and about 1:5. It will berecognized, however, that if it is desired to reduce to a minimum theamount of unreacted hydrogen halide requiring neutralization uponcompletion of the reaction, hydrogen halide concentrations toward thelower molar ratio limit may be preferred.

In any event, the concentration of the anhydrous hydrogen halide needonly be sufficient to permit the desired production of the2-haloaldehyde acetal product to proceed at a reasonable rate.

The electrolysis of the present process can be conducted at a broadrange of temperatures--ambient, or higher or lowertemperatures--although as noted hereinabove, temperatures of less than30° C. tend to favor production of unsubstituted acetal product (albeitin minor amounts). For convenience, temperature ranges from about 0° C.and about 100° C. are suitable, with the range between about 30° C. andabout 75° C. being preferred.

If volatile material--low molecular weight primary alcohols (C₂ -C₄) andadded solvents of methylene chloride or methanol--are employed, it maybe desirable to avoid elevated temperatures greater than the preferredhigher temperature so that these materials will not escape. Variouscooling means can be used for this purpose. The amount of coolingcapacity needed for the desired degree of control will depend upon thecell resistance and the electrical current drawn. If desired, coolingcan be effected by permitting a component to reflux through a coolingcondenser, or by immersing the electrolytic cell in a cold water bath,or an ice or ice-salt bath. Pressure can be employed to permitelectrolysis at higher temperatures with volatile components, butunnecessary employment of pressure is usually undesirable from aneconomic standpoint.

The process of the present invention can be conducted at atmosphericpressure, super atmospheric pressures, and subatmospheric pressures. Forreasons of economy and ease of construction of the equipment employed inthe present process it is preferred to conduct this process atatmospheric pressure. As noted hereinabove, however, pressure (superatmospheric pressures) can be employed to permit electrolysis at highertemperatures with volatile components.

Various current densities can be employed in the present process. Itwill be desirable to employ high current densities in order to achievehigh use of electrolytic cell capacity which will result in increasedpayload. Therefore, for production purposes it will generally bedesirable to use as high a density as feasible, taking intoconsideration sources and cost of electrical current, resistance of theelectrolysis medium, heat dissipation, effect upon yields, and the like.Over broad range of current density, the density will not greatly affectyield. And while low densities are operable, suitable ranges forefficient operation will generally be in the range of a few hundredamperes per square meter of anode surface up to 10,000 or more amperesper square meter.

In effecting the present process, the cell voltage must be sufficient topass the desired current (amperes) and to effect anodic oxidation of thehydrogen halide. It will be recognized, however, that the cell voltagewill vary with electrode materials and their surface condition, thedistance between the electrodes, various materials in the electrolysismedium, resistance of the electrolysis medium, and the like. Forexample, under the conditions employed in the illustrative Examplesdescribed hereinbelow, the cell voltage ranges between about +4.0 voltsand about +36 volts.

The present process can be conducted in the various types ofelectrolytic cells known in the art. In general, such cells comprise acontainer made of material capable of resisting action of electrolytes,that is, material which is inert under the reaction conditions, forexample, glass or plastic, and one or more anodes and cathodes connectedto a source of direct electric current such as a battery and the like.The anode may be of any electrode material so long as it is relativelyinert under the reaction conditions. Suitable anode materials include,for example, graphite, de Nora-type dimensionally stable anodes, theprecious metals such as platinum, palladium, ruthenium, rhodium, and thelike, and the precious metals plated onto other metals, such as, forexample, titanium and tantulum. The precious metal type anodes, however,suffer from the disadvantages of being relatively expensive and somewhatsusceptible to corrosion under reaction conditions.

The de Nora-type dimensionally stable anodes employ precious metaloxides plated on a titanium substrate. Other materials include, forexample, ruthenium oxide, mixed with oxides of titanium and tantalum,also plated on a titanium substrate. Dimensionally stable anodessuitable for use in the present process are currently commerciallyavailable from the Diamond Shamrock Company, Cleveland, Ohio 44114.

The anode materials of choice are graphite and de Nora-typedimensionally stable anodes, with graphite generally being preferred. Itwill be recognized, however, that it may be advantageous to employ deNora-type anodes under long-term conditions where anode corrosion mayoccur. A further advantage resulting from the use of dimensionallystable anodes is the lowering of the halogen overvoltage with aconcurrent lowering of energy requirements.

Any suitable electrode material may be employed as the cathode so longas it is relatively inert under the reaction conditions and does notpromote the production of undesirable by-products. Graphite servesadmirably as the cathode material of choice. Low hydrogen overvoltagemetals, such as, for example, platinum, palladium, and the like are alsosuitable as cathode materials, although, as noted hereinabove, theysuffer from the disadvantage of being relatively expensive.

In the present process, either an undivided or a divided cell can beemployed. An undivided cell, however, is generally preferred in thatelectrical resistance across a cell divider is eliminated. This, ofcourse, could have advantages for industrial production.

A divided cell contains a suitable barrier material or separator whichwill prevent the free flow of reactants between the cathode and theanode. Generally, the separator is some mechanical barrier which isrelatively inert to electrolyte material, for example, a fritted glassfilter, glass cloth, asbestos, and the like but will permit the passageof current to complete the electrical circuit.

When a divided cell is used, it will be possible to employ the sameelectrolysis medium on both the anode and cathode sides, or to employdifferent media. Ordinarily, it will be desirable to employ the samemedium on both the anode and cathode sides; however, in somecircumstances, it may be desirable to employ a different catholyte foreconomy of materials, lower electrical resistance, and the like.

As noted hereinabove, however, an undivided cell is preferred for use inthe present process.

The electrolytic cells employed in the illustrative Examples herein areprimarily for laboratory demonstration purposes. Production cells areusually designed with a view to the economics of the process, andcharacteristically have large electrode surfaces and short distancesbetween the electrodes.

For a general description of various laboratory scale cells, see Lund etal, "Practical Problems in Electrolysis," in Organic Electrochemistry(Baizer, ed.), Marcel Dekker, New York, 1973, pp. 165-249, and for someconsiderations of industrial cell designs, see Danly, "IndustrialElectroorganic Chemistry," in Ibid., pp. 907-946.

The 2-haloaldehyde acetal products obtained in the present process areisolated by neutralization of the reaction mixture with excess calciumcarbonate (alkali metal carbonates, for example, sodium carbonate, mayalso be used, but are less effective in that they become coated withalkali metal halide), filtration, and atmospheric-pressure distillationof the unreacted primary alcohol and/or added solvent to give a mixtureof the crude product and calcium halide. This mixture is partitionedbetween water and a suitable water immiscible organic solvent, forexample, diethyl ether and the organic solvent separated, washed withwater, dried over an appropriate dessicant, for example, anhydrouscalcium sulfate, filtered, and evaporated to give the crude product. Thecrude product is distilled at appropriate temperatures and pressures toyield the pure acetal of the 2-haloaldehyde.

Varying amounts of by-products are produced during the present processin addition to the desired 2-haloaldehyde acetal product. Theseby-products include the unsubstituted (non-halogenated) acetal, thedihaloacetal (for primary alcohols having two or three beta hydrogenatoms), and the trihaloacetal (from ethanol which has three betahydrogen atoms). The relative importance of these by-products depends,as noted hereinabove, on reaction temperature, hydrogen halideconcentration, and, in addition, substrate primary alcohol conversion.Since low temperature, as well as low hydrogen halide concentrations,favor production of the unsubstituted acetal, the process is generallycarried out at the preferred temperature ranges and within the preferredhydrogen halide to primary alcohol molar ratio ranges.

As noted hereinabove, however, if it is desired to reduce to a minimumthe amount of unreacted hydrogen halide to be neutralized followingcompletion of the reaction, it is possible to use a low hydrogen halideconcentration and pass sufficient current to consume almost all of it.The most abundant by-product under these conditions, the unsubstitutedacetal, may be recycled with the unreacted primary alcohol and/or addedsolvent for further reaction.

The effect of conversion on the production of by-products is morecomplex than the temperature and hydrogen halide concentration factors.As the conversion increases, selectivity to the monohaloacetal productdecreases--albeit to a constant value which is quite high (Examples 5-8,Table 1)--due to increased dihaloacetal formation (Examples 3-5, Table1). However, while the selectivity reaches a constant value, there is aprogressive decline in current efficiency (Examples 3-8, Table 1). As aresult, it is generally desirable to use fairly low conversions.

The term "selectivity" is employed herein to mean the amount ofmonohaloaldehyde acetal product expressed as a percentage of the totalmoles of all acetal products.

Other minor by-products include the corresponding ester, for example,ethyl acetate from ethanol and n-butyl butyrate from n-butyl alcohol.This becomes the major product when substantial amounts of water arepresent in the electrolysis medium, for example, when concentratedaqueous hydrogen halide is substituted for the anhydrous hydrogenhalide. For this reason, the presence of water in greater than nominalamounts is to be avoided and a substantially anhydrous electrolysismedium is employed.

The following examples illustrate the process of the present invention.They are not to be construed as limitative upon the overall scopethereof.

EXAMPLE 1

A 1-liter, 3-necked, round-bottomed flask equipped with a magneticstirrer; two graphite-rod electrodes (12 inches × 0.25 inch diameter;30.48 centimeters × 0.635 centimeter diameter) inserted, via two 10/18standard taper joint Teflon thermometer adaptors, into a glass electrodeadaptor having two 10/18 standard taper joints and one 34/50 standardtaper joint; a water-cooled reflux condenser, topped with a liquidparaffin bubbler in one 24/40 standard taper joint side neck; and a10/18 standard taper joint thermometer placed in the remaining side neckvia a 10/18-24/40 glass adaptor so as to extend into the electrolysismedium was used as an electrolytic cell. The graphite-rod electrodeswere adjusted until they projected as far into the flask as possible,without interfering with the operation of the magnetic stirring bar.

Absolute ethanol (230.0 grams, 5.00 moles) and 38.0 grams (1.04 moles)of hydrogen chloride (via an immersed glass frit-tipped gas bubblerwhich was subsequently removed and replaced by the thermometer) werecharged to the electrolytic cell which was thereafter partially immersedin a bath of flowing cold water. The resultant solution was electrolyzedat a constant current of 1.5 amperes for 18 hours (which is equivalentto 27.0 ampere-hours which equal 1.01 faradays). The cell voltage wasinitially 4.0 volts and rose slowly to 4.5 volts. The temperature of theelectrolyte solution was 30°-32° C. A small portion (about 1 percent byweight) of the electrolyzed solution was withdrawn and analyzed bynuclear magnetic resonance spectroscopy. By integration of the tripletacetal proton resonance [ClCH₂ CH(OCH₂ CH₃)₂ ] and the triplet resonanceof a known added quantity of 1,1,2-trichloroethane, it was determinedthat 0.20 mole of chloroacetal had been formed.

The electrolyzed solution was neutralized by stirring with excesscalcium carbonate. The neutralized solution was filtered and the solidresidue washed with ethanol. The combined filtrate and washings weredistilled to remove most of the ethanol (boiling point 77°-79° C.). Theresidue was cooled and partitioned between diethyl ether and water. Theether solution was washed with water and dried over anhydrous calciumsulfate. The filtered ether solution was distilled, collecting thefraction with boiling point 156°-160° C., which was identified aschloroacetal (24.1 grams; 0.16 mole; 63 percent efficiency).

The product was identified by comparison with an authentic sample and byits reaction with 2,4-dinitrophenylhydrazine dissolved in concentratedhydrochloric acid which afforded chloracetaldehyde2,4-dinitrophenylhydrazone, melting point 158°-159° C. (literaturemelting point 158° C.).

EXAMPLE 2

The electrolytic cell described in EXAMPLE 1 was employed. A solution of20.0 grams (0.55 mole) of anhydrous hydrogen chloride in 296 grams (4.00mole) of anhydrous n-butyl alcohol was charged to the cell andelectrolyzed with a current of 1.0 ampere for 13.4 hours (which isequivalent to 13.4 ampere-hours which equal 0.50 faraday) following theprocedure of EXAMPLE 1. The initial and final cell voltages andtemperatures were 18 volts and 27 volts and 30° C. and 32° C.,respectively. Work up of the electrolyzed solution afforded 28.5 gramsof a colorless oil which was distilled in vacuo to give two fractions:(1) a water-white liquid (12.0 grams), boiling point 65°-70° C./0.05millimeter of mercury and (2) a water-white liquid (13.5 grams), boilingpoint 72°-73° C./0.04 millimeter of mercury. The latter fraction[fraction (2)] was identified as 2-chloro-n-butyraldehyde di-n-butylacetal. Elemental analysis indicated carbon and hydrogen contents of60.90 and 10.90 percent, respectively, as compared with the theoreticalcontents of 60.89 and 10.57 percent calculated for2-chloro-n-butyraldehyde di-n-butyl acetal (C₁₂ H₂₅ ClO₂). The firstfraction was also 2-chloro-n-butyraldehyde di-n-butyl acetalcontaminated with about 10 mole percent of n-butyraldehyde di-n-butylacetal as estimated by nuclear magnetic resonance spectroscopy.

The current efficiency for total isolated 2-chloro-n-butyraldehydedi-n-butyl acetal was estimated at 82 percent.

EXAMPLE 3

The electrolytic cell and procedure described in EXAMPLE 2 was employedusing 40.0 grams (1.10 moles) of anhydrous hydrogen chloride. Thesolution was electrolyzed with a current of 1.5 amperes at a temperatureof 35°-40° C. until 0.40 faraday had passed. Isolation of the productyielded 19.6 grams (0.083 mole; 83 percent current efficiency; 95percent selectivity) of 2-chloro-n-butyraldehyde di-n-butyl acetal and1.1 grams (0.004 mole; 6 percent current efficiency) of2,2-dichloro-n-butyraldehyde di-n-butyl acetal. A trace ofn-butyraldehyde di-n-butyl acetal was also detected.

EXAMPLES 4-8

The electrolytic cell and procedure described in EXAMPLE 3 above wasemployed except that electric current (1.5 amperes) was passed forincrementally longer periods of time to pass 0.80, 1.20, 1.68, 2.00, and2.36 faradays, respectively, for EXAMPLES 4, 5, 6, 7 and 8. The resultsare tabulated in TABLE 1.

EXAMPLE 9

The electrolytic cell and procedure described in EXAMPLE 3 was repeatedusing 75.2 grams (2.06 moles) of anhydrous hydrogen chloride. Thereaction temperature was 35°-36° C. The results are tabulated in TABLE1.

EXAMPLE 10

The electrolytic cell described in EXAMPLE 1 was charged with 296.0grams (4.00 mole) of anhydrous n-butyl alcohol and 40.0 grams (0.50mole) of anhydrous hydrogen bromide. The resultant solution waselectrolyzed at a constant current of 1.0 ampere for 26.8 hours (whichis equivalent to 26.8 ampere-hours which equal 1.0 faraday). After abrief initial period, the temperature of the electrolyte solutionreached 58° C. and thereafter increased only slowly to reach 60° C. atthe end of the electrolysis period. Throughout this period the color ofbromine persisted in the solution. The electrolyzed solution was allowedto cool to ambient temperatures (during which time the color of brominedisappeared) and treated as described in EXAMPLE 1, giving 23.8 grams ofa yellow oil. Distillation at 0.01 millimeter of mercury pressure gave14.9 grams of 2-bromo-n-butyraldehyde di-n-butyl acetal, boiling point67°-69° C.; 2.2 grams of a mixed fraction, boiling point 69°-83° C.; and3.7 grams of 2,2-dibromo-n-butyraldehyde di-n-butyl acetal, boilingpoint 83°-87° C.

The current efficiencies for the total yield of 2-bromo-n-butyraldehydedi-n-butyl acetal and 2,2-dibromo-n-butyraldehyde di-n-butyl acetal were23 percent and 8 percent, respectively.

EXAMPLE 11

The electrolytic cell and procedure described in EXAMPLE 10 was employedexcept that instead of hydrogen bromide, 64.0 grams (0.50 mole) ofanhydrous hydrogen iodide was employed. No identifiable products wereobtained.

EXAMPLE 12

A solution of 74.0 grams (1.00 mole) of anhydrous n-butyl alcohol in 200milliliters of methylene chloride was charged to the electrolytic celldescribed in EXAMPLE 1 and saturated with anhydrous hydrogen chloride.The solution was electrolyzed at a constant current of 0.8 ampere for3.33 hours (which is equivalent to 2.7 ampere-hours which equal 0.1faraday) with a cell voltage of 32-36 volts while maintaining a slowstream of anhydrous hydrogen chloride therethrough. The passage ofcurrent maintained the solution at reflux. The electrolyzed solution wasneutralized by stirring overnight (approximately 16 hours) with excesscalcium carbonate. The neutralized solution was filtered and themethylene chloride removed by evaporation. The liquid residue wasanalyzed by gas-liquid chromatography which showed the presence of2-chloro-n-butyraldehyde di-n-butyl acetal (4.7 grams; 0.020 mole 80percent current efficiency) and 2,2-dichloro-n-butyraldehyde di-n-butylacetal (0.071 gram; 0.00030 mole; 2 percent current efficiency).

EXAMPLE 13

A solution of 74.0 grams (1.00 mole) of anhydrous isobutyl alcohol and86.0 grams (2.08 moles) of anhydrous hydrogen chloride in 256.0 grams(8.0 moles) of absolute methanol was charged to the electrolytic celldescribed in EXAMPLE 1 and electrolyzed at a constant current of 4.0amperes for 26.8 hours (which is equivalent to 107.2 ampere-hours whichequal 4.00 faradays). The solution was clear and colorless throughoutthe electrolysis period. The temperature of the electrolyte solution was35°-40° C. and the cell voltage 14-17 volts.

The electrolyzed solution was neutralized by stirring with excesscalcium carbonate. The neutralized solution was filtered and the solidresidue washed with methanol. A portion (1 percent by weight) of thecombined filtrate and washings was reserved for gas-liquidchromatographic analysis. The remainder was evaporated to remove themethanol. The residue was partitioned between diethyl ether and water.The ether layer was separated, washed with water, dried over anhydrouscalcium sulfate, filtered, and evaporated. The residue was distilled,collecting the fraction with boiling point 144°-149° C. This materialwas identified by nuclear magnetic resonance spectroscopy as2-chloroisobutyraldehyde dimethyl acetal (63.0 grams; 0.41 mole; 45percent current efficiency) by its nuclear magnetic resonance spectrumin deuterochloroform solution (singlet resonances at 1.50, 3.53 and 4.13parts per million downfield from an internal tetramethylsilanereference, due to the C-methyls, O-methyls and acetal proton,respectively).

As a further confirmation of the identity of the isolated product, asmall portion was reacted with 2,4-dinitrophenylhydrazine dissolved inconcentrated hydrochloric acid to afford 2-chloroisobutyraldehyde2,4-dinitrophenylhydrazone. Elemental analysis indicated carbon,hydrogen, chlorine, and nitrogen contents of 42.30, 4.40, 12.20, and19.90 percent, respectively, as compared with the theoretical contentsof 41.88, 3.84, 12.39, and 19.55 percent calculated for2-chloroisobutyraldehyde 2,4-dinitrophenylhydrazone (C₁₀ H₁₁ ClN₄ O₄).

The isolated product was redistilled, taking a center cut with boilingpoint 145°-146° C. Using this material as a standard for gas-liquidchromatographic analysis, it was determined that the total amount of2-chloroisobutyraldehyde dimethyl acetal formed was 0.61 mole (61percent current efficiency) by analysis of the reserved sample of theneutralized reaction mixture.

EXAMPLE 14

The electrolytic cell described in EXAMPLE 1 was employed. A solution of35.8 (0.98 mole) of anhydrous hydrogen chloride in 256.0 grams (8.00moles) of absolute methanol was charged to the cell and electrolyzedwith a constant current of 4.0 amperes for 10.75 hours (which isequivalent to 43.0 ampere-hours which equal 1.60 faradays). During theelectrolysis the temperature of the solution was maintained at 28° C. bywater cooling and the cell voltage was constant at 12 volts. Throughoutmost of the electrolysis period the green color of anodically generatedchlorine was evident in the solution.

The electrolyzed solution was examined by nuclear magnetic resonancespectroscopy which showed the presence of methyl formate [HCOOCH₃resonance at 4.70 parts per million downfield from CH₃ OH resonance,HCOOCH₃ resonance at 0.35 parts per million downfield from CH₃ OHresonance] and methylal [CH₂ (OCH₃)₂ resonance 1.17 parts per milliondownfield from CH₃ OH resonance]. The solution was neutralized withexcess calcium carbonate, filtered, and analyzed by gas-liquidchromatography. Methyl formate (2.4 grams; 0.040 mole; 5 percent currentefficiency) and methylal (1.4 grams; 0.019 mole; 4.8 percent currentefficiency) were shown to be present.

The parameters and results for EXAMPLES 1-14 are summarized andtabulated in TABLE 1. It will be noted that EXAMPLE 14 is included todemonstrate the resistance of methanol to oxidation under processconditions.

                                      TABLE 1                                     __________________________________________________________________________    The Formation of Acetals via Electrolysis of Anhydrous Alcohols in the        Presence of Anhydrous Hydrogen Halides.                                                                          Electricity           Selectivity                                    Current                                                                            Temp.                                                                             Passed                                                                              [mmoles (current                                                                              to Mono.sup.b        Ex.                                                                              Alcohol                                                                             (moles)                                                                           Solvent.sup.a                                                                      Halide                                                                            (moles)                                                                           (A)  (° C)                                                                      (F)   Unsubs                                                                             Monohalo                                                                            Dihalo                                                                             (%)                  __________________________________________________________________________     1.                                                                              C.sub.2 H.sub.5 OH                                                                  (5.00)   HCl (1.04)                                                                            2.0  32-3                                                                              1.00  4 (1)                                                                              201 (80)                                                                            7 (4)                                                                              95                    2.                                                                              n-C.sub.4 H.sub.9 OH                                                                (4.00)   HCl (0.55)                                                                            1.0  30-2                                                                              0.50  6 (2)                                                                              103 (82)                                                                            trace                                                                              95                    3.                                                                              n-C.sub.4 H.sub.9 OH                                                                (4.00)   HCl (1.10)                                                                            1.5  35-40                                                                             0.40  trace                                                                              83 (83)                                                                             4 (6)                                                                              95                    4.                                                                              n-C.sub.4 H.sub.9 OH                                                                (4.00)   HCl (1.10)                                                                            1.5  35-40                                                                             0.80  trace                                                                              154 (77)                                                                            15 (11)                                                                            91                    5.                                                                              n-C.sub.4 H.sub.9 OH                                                                (4.00)   HCl (1.10)                                                                            1.5  35-40                                                                             1.20  trace                                                                              204 (68)                                                                            31 (16)                                                                            84                    6.                                                                              n-C.sub.4 H.sub.9 OH                                                                (4.00)   HCl (1.10)                                                                            1.5  35-40                                                                             1.68  trace                                                                              268 (64                                                                             44 (16)                                                                            86                    7.                                                                              n-C.sub.4 H.sub.9 OH                                                                (4.00)   HCl (1.10)                                                                            1.5  35-40                                                                             2.00  trace                                                                              276 (56)                                                                            51 (15)                                                                            84                    8.                                                                              n-C.sub.4 H.sub.9 OH                                                                (4.00)   HCl (1.10)                                                                            1.5  35-40                                                                             2.36  trace                                                                              289 (34)                                                                            56 (10)                                                                            84                    9.                                                                              n-C.sub.4 H .sub.9 OH                                                               (4.00)   HCl (2.06)                                                                            1.5  35-6                                                                              0.40  trace                                                                              76 (76)                                                                             8 (12)                                                                             90                   10.                                                                              n-C.sub.4 H.sub.9 OH                                                                (4.00)   HBr (0.50)                                                                            1.0  58-60                                                                             1.00  trace                                                                              57 (23)                                                                             13 (8)                                                                             81                      n-C.sub.4 H.sub.9 OH                                                                (4.00)   HI  (0.50)                                                                            1.0  58-60                                                                             1.00   --   --    --  --                      n-C.sub.4 H.sub.9 OH                                                                (1.00)                                                                            CH.sub.2 Cl.sub.2.sup.c                                                            HCl (satd.)                                                                           0.8  38-40                                                                             0.10  trace                                                                              20 (80)                                                                             0.3                                                                                99)                     iso-C.sub.4 H.sub.9 OH                                                              (1.00)                                                                            CH.sub.3 OH.sup.d                                                                  HCl (2.08)                                                                            4.0  35-40                                                                             4.0   nd.sup.e                                                                           610 (61).sup.f                                                                       --  --                   14..sup.g                                                                        CH.sub.3 OH                                                                         (8.00)   HCl (0.98)                                                                            4.0  28  1.60  40 (5)                                                                              --    --  --                   __________________________________________________________________________     .sup.a Apart from excess alcohol.                                             .sup.b Monosubstituted acetal as a percentage of all three (mole basis).      .sup.c 200 ml.                                                                .sup.d 256 g. (8.0 moles).                                                    .sup.e No attempt made to detect this compound.                               .sup.f Product is 2-chloroisobutyraldehyde dimethyl acetal.                   .sup.g Methyl formate, 19 mmoles (5 percent current efficiency), also         formed.                                                                  

The acetals of 2-haloacetals have a number of useful purposes. As notedhereinabove, such compounds are versatile bifunctional reagents whichcan react either as alkyl halides or as sources of an aldehyde, or both.They are particularly useful intermediates in the synthesis ofsulfathiazole and substituted derivatives thereof. For example, theformer compound, sulfathiazole--a well known sulfa drug, is readilyprepared by reaction of chloroacetal (chloroacetaldehyde diethyl acetal)with p-acetamidobenzenesulfonylthiourea followed by alkaline hydrolysisof the resulting p-acetamidobenzenesulfonamidothiazole to remove theN-acetyl group.

While the invention has been described with respect to various specificexamples and embodiments thereof, it is to be understood that theinvention is not limited thereto and that many alternatives,modifications, and variations will be apparent to those skilled in theart in light of the foregoing description. Accordingly, it is intendedto embrace all such alternatives, modifications, and variations as fallwithin the spirit and broad scope of the invention.

What is claimed is:
 1. A process for the preparation of acetals of2-haloaldehydes which comprises subjecting a substantially anhydrousliquid electrolysis medium comprising a primary alcohol having at leastone beta hydrogen atom and an anhydrous hydrogen halide selected fromthe group consisting of hydrogen chloride and hydrogen bromide toelectrolysis in an electrolytic cell to yield the acetal of the2-haloaldehyde corresponding to the primary alcohol.
 2. The process ofclaim 1 wherein the primary alcohol is ethanol.
 3. The process of claim1 wherein the primary alcohol is n-butyl alcohol.
 4. The process ofclaim 1 wherein the primary alcohol is isobutyl alcohol.
 5. The processof claim 1 wherein the primary alcohol is ethanol, the anhydroushydrogen halide is hydrogen chloride, and the acetal of the2-haloaldehyde is chloroacetaldehyde diethyl acetal.
 6. The process ofclaim 1 wherein the primary alcohol is n-butyl alcohol, the anhydroushydrogen halide is hydrogen chloride, and the acetal of the2-haloaldehyde is 2-chloro-n-butyraldehyde di-n-butyl acetal.
 7. Theprocess of claim 1 wherein the primary alcohol is n-butyl alcohol, theanhydrous hydrogen halide is hydrogen bromide, and the acetal of the2-haloaldehyde is 2-bromo-n-butyraldehyde di-n-butyl acetal.
 8. Theprocess of claim 1 wherein the molar ratio of anhydrous hydrogen halideto the primary alcohol is between about 1:0.1 and about 1:10.
 9. Theprocess of claim 1 wherein the reaction temperature is between about 0°C. and about 100° C.
 10. The process of claim 1 wherein a graphite anodeand a graphite cathode are used.
 11. The process of claim 1 wherein theelectrolytic cell is an undivided cell.
 12. The process of claim 1wherein the liquid electrolysis medium contains an added solvent. 13.The process of claim 12 wherein the added solvent is selected from thegroup consisting of methanol and methylene chloride.
 14. A process forthe preparation of dimethyl acetals of 2-haloaldehydes which comprisessubjecting a substantially anhydrous liquid electrolysis mediumcomprising a primary alcohol having at least one beta hydrogen atom,anhydrous hydrogen halide selected from the group consisting of hydrogenchloride and hydrogen bromide, and methanol to electrolysis in anelectrolytic cell to yield the dimethyl acetal of the 2-haloaldehydecorresponding to the primary alcohol.
 15. The process of claim 14wherein the concentration of the primary alcohol in methanol is betweenabout 1.0 molar and about 6.0 molar; the molar ratio of the hydrogenhalide to the primary alcohol is between about 1:0.1 and about 1:10, andthe reaction temperature is between about 0° C. and about 100° C. 16.The process of claim 14 wherein the primary alcohol is isobutyl alcohol,the anhydrous hydrogen halide is hydrogen chloride, and the dimethylacetal of the 2-haloaldehyde is 2-chloroisobutyraldehyde dimethylacetal.